Auxotrophy to Xeno-DNA : an exploration of combinatorial mechanisms for a high-fidelity biosafety system for synthetic biology applications

Lade...
Vorschaubild
Dateien
Whitford_2-1i6yf0dys6dlm9.pdf
Whitford_2-1i6yf0dys6dlm9.pdfGröße: 1.99 MBDownloads: 3622
Datum
2018
Autor:innen
Whitford, Christopher M.
Dymek, Saskia
März, Camilla
Schmidt, Olga
Edich, Maximilian
Droste, Julian
Pucker, Boas
Rückert, Christian
Kalinowski, Jörn
Herausgeber:innen
Kontakt
ISSN der Zeitschrift
Electronic ISSN
ISBN
Bibliografische Daten
Verlag
Schriftenreihe
Auflagebezeichnung
ArXiv-ID
Internationale Patentnummer
Link zur Lizenz
Angaben zur Forschungsförderung
Projekt
Open Access-Veröffentlichung
Open Access Gold
Sammlungen
Core Facility der Universität Konstanz
Gesperrt bis
Titel in einer weiteren Sprache
Forschungsvorhaben
Organisationseinheiten
Zeitschriftenheft
Publikationstyp
Zeitschriftenartikel
Publikationsstatus
Published
Erschienen in
Journal of Biological Engineering. 2018, 12(1), 13. eISSN 1754-1611. Available under: doi: 10.1186/s13036-018-0105-8
Zusammenfassung

Background
Biosafety is a key aspect in the international Genetically Engineered Machine (iGEM) competition, which offers student teams an amazing opportunity to pursue their own research projects in the field of Synthetic Biology. iGEM projects often involve the creation of genetically engineered bacterial strains. To minimize the risks associated with bacterial release, a variety of biosafety systems were constructed, either to prevent survival of bacteria outside the lab or to hinder horizontal or vertical gene transfer.

Main body
Physical containment methods such as bioreactors or microencapsulation are considered the first safety level. Additionally, various systems involving auxotrophies for both natural and synthetic compounds have been utilized by iGEM teams in recent years. Combinatorial systems comprising multiple auxotrophies have been shown to reduced escape frequencies below the detection limit. Furthermore, a number of natural toxin-antitoxin systems can be deployed to kill cells under certain conditions. Additionally, parts of naturally occurring toxin-antitoxin systems can be used for the construction of ‘kill switches’ controlled by synthetic regulatory modules, allowing control of cell survival. Kill switches prevent cell survival but do not completely degrade nucleic acids. To avoid horizontal gene transfer, multiple mechanisms to cleave nucleic acids can be employed, resulting in ‘self-destruction’ of cells. Changes in light or temperature conditions are powerful regulators of gene expression and could serve as triggers for kill switches or self-destruction systems. Xenobiology-based containment uses applications of Xeno-DNA, recoded codons and non-canonical amino acids to nullify the genetic information of constructed cells for wild type organisms. A ‘minimal genome’ approach brings the opportunity to reduce the genome of a cell to only genes necessary for survival under lab conditions. Such cells are unlikely to survive in the natural environment and are thus considered safe hosts. If suitable for the desired application, a shift to cell-free systems based on Xeno-DNA may represent the ultimate biosafety system.

Conclusion
Here we describe different containment approaches in synthetic biology, ranging from auxotrophies to minimal genomes, which can be combined to significantly improve reliability. Since the iGEM competition greatly increases the number of people involved in synthetic biology, we will focus especially on biosafety systems developed and applied in the context of the iGEM competition.

Zusammenfassung in einer weiteren Sprache
Fachgebiet (DDC)
570 Biowissenschaften, Biologie
Schlagwörter
Kill switch, iGEM, Semantic containment, Physical containment, Auxotrophy, Escherichia coli, BioBrick, Genetic engineering
Konferenz
Rezension
undefined / . - undefined, undefined
Zitieren
ISO 690WHITFORD, Christopher M., Saskia DYMEK, Denny KERKHOFF, Camilla MÄRZ, Olga SCHMIDT, Maximilian EDICH, Julian DROSTE, Boas PUCKER, Christian RÜCKERT, Jörn KALINOWSKI, 2018. Auxotrophy to Xeno-DNA : an exploration of combinatorial mechanisms for a high-fidelity biosafety system for synthetic biology applications. In: Journal of Biological Engineering. 2018, 12(1), 13. eISSN 1754-1611. Available under: doi: 10.1186/s13036-018-0105-8
BibTex
@article{Whitford2018Auxot-48115,
  year={2018},
  doi={10.1186/s13036-018-0105-8},
  title={Auxotrophy to Xeno-DNA : an exploration of combinatorial mechanisms for a high-fidelity biosafety system for synthetic biology applications},
  number={1},
  volume={12},
  journal={Journal of Biological Engineering},
  author={Whitford, Christopher M. and Dymek, Saskia and Kerkhoff, Denny and März, Camilla and Schmidt, Olga and Edich, Maximilian and Droste, Julian and Pucker, Boas and Rückert, Christian and Kalinowski, Jörn},
  note={Article Number: 13}
}
RDF
<rdf:RDF
    xmlns:dcterms="http://purl.org/dc/terms/"
    xmlns:dc="http://purl.org/dc/elements/1.1/"
    xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
    xmlns:bibo="http://purl.org/ontology/bibo/"
    xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#"
    xmlns:foaf="http://xmlns.com/foaf/0.1/"
    xmlns:void="http://rdfs.org/ns/void#"
    xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > 
  <rdf:Description rdf:about="https://kops.uni-konstanz.de/server/rdf/resource/123456789/48115">
    <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/48115"/>
    <dc:creator>Kalinowski, Jörn</dc:creator>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
    <dc:creator>Droste, Julian</dc:creator>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/43"/>
    <dc:contributor>Dymek, Saskia</dc:contributor>
    <dcterms:abstract xml:lang="eng">Background&lt;br /&gt;Biosafety is a key aspect in the international Genetically Engineered Machine (iGEM) competition, which offers student teams an amazing opportunity to pursue their own research projects in the field of Synthetic Biology. iGEM projects often involve the creation of genetically engineered bacterial strains. To minimize the risks associated with bacterial release, a variety of biosafety systems were constructed, either to prevent survival of bacteria outside the lab or to hinder horizontal or vertical gene transfer.&lt;br /&gt;&lt;br /&gt;Main body&lt;br /&gt;Physical containment methods such as bioreactors or microencapsulation are considered the first safety level. Additionally, various systems involving auxotrophies for both natural and synthetic compounds have been utilized by iGEM teams in recent years. Combinatorial systems comprising multiple auxotrophies have been shown to reduced escape frequencies below the detection limit. Furthermore, a number of natural toxin-antitoxin systems can be deployed to kill cells under certain conditions. Additionally, parts of naturally occurring toxin-antitoxin systems can be used for the construction of ‘kill switches’ controlled by synthetic regulatory modules, allowing control of cell survival. Kill switches prevent cell survival but do not completely degrade nucleic acids. To avoid horizontal gene transfer, multiple mechanisms to cleave nucleic acids can be employed, resulting in ‘self-destruction’ of cells. Changes in light or temperature conditions are powerful regulators of gene expression and could serve as triggers for kill switches or self-destruction systems. Xenobiology-based containment uses applications of Xeno-DNA, recoded codons and non-canonical amino acids to nullify the genetic information of constructed cells for wild type organisms. A ‘minimal genome’ approach brings the opportunity to reduce the genome of a cell to only genes necessary for survival under lab conditions. Such cells are unlikely to survive in the natural environment and are thus considered safe hosts. If suitable for the desired application, a shift to cell-free systems based on Xeno-DNA may represent the ultimate biosafety system.&lt;br /&gt;&lt;br /&gt;Conclusion&lt;br /&gt;Here we describe different containment approaches in synthetic biology, ranging from auxotrophies to minimal genomes, which can be combined to significantly improve reliability. Since the iGEM competition greatly increases the number of people involved in synthetic biology, we will focus especially on biosafety systems developed and applied in the context of the iGEM competition.</dcterms:abstract>
    <dcterms:issued>2018</dcterms:issued>
    <dc:contributor>Rückert, Christian</dc:contributor>
    <dc:contributor>Schmidt, Olga</dc:contributor>
    <dc:language>eng</dc:language>
    <dc:creator>März, Camilla</dc:creator>
    <dc:creator>Whitford, Christopher M.</dc:creator>
    <dc:contributor>Droste, Julian</dc:contributor>
    <dc:rights>Attribution 4.0 International</dc:rights>
    <dcterms:title>Auxotrophy to Xeno-DNA : an exploration of combinatorial mechanisms for a high-fidelity biosafety system for synthetic biology applications</dcterms:title>
    <dc:creator>Dymek, Saskia</dc:creator>
    <dc:contributor>Kerkhoff, Denny</dc:contributor>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2019-12-19T09:24:17Z</dc:date>
    <dc:creator>Schmidt, Olga</dc:creator>
    <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/48115/1/Whitford_2-1i6yf0dys6dlm9.pdf"/>
    <dc:contributor>Kalinowski, Jörn</dc:contributor>
    <dc:contributor>März, Camilla</dc:contributor>
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
    <dc:creator>Edich, Maximilian</dc:creator>
    <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/48115/1/Whitford_2-1i6yf0dys6dlm9.pdf"/>
    <dc:contributor>Edich, Maximilian</dc:contributor>
    <dcterms:rights rdf:resource="http://creativecommons.org/licenses/by/4.0/"/>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2019-12-19T09:24:17Z</dcterms:available>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/43"/>
    <dc:contributor>Whitford, Christopher M.</dc:contributor>
    <dc:creator>Pucker, Boas</dc:creator>
    <dc:contributor>Pucker, Boas</dc:contributor>
    <dc:creator>Kerkhoff, Denny</dc:creator>
    <dc:creator>Rückert, Christian</dc:creator>
  </rdf:Description>
</rdf:RDF>
Interner Vermerk
xmlui.Submission.submit.DescribeStep.inputForms.label.kops_note_fromSubmitter
Kontakt
URL der Originalveröffentl.
Prüfdatum der URL
Prüfungsdatum der Dissertation
Finanzierungsart
Kommentar zur Publikation
Allianzlizenz
Corresponding Authors der Uni Konstanz vorhanden
Internationale Co-Autor:innen
Universitätsbibliographie
Nein
Begutachtet
Ja
Diese Publikation teilen